Multiple myeloma: update on pathophysiology and management

Abstract

Proteasome inhibitors and immunomodulatory drugs have substantially improved the clinical outcomes in patients with multiple myeloma (MM) since 2000. In 2015, the new monoclonal antibodies, daratumumab and elotuzumab, were approved for treating relapsed and/or refractory MM (RRMM). Furthermore, venetoclax, a selective BCL-2 inhibitor, and chimeric antigen receptor (CAR) T-cell therapy that work against B-cell maturation antigen (BCMA) have reportedly shown great efficacy in phase 1 studies. The efficacy of venetoclax has been observed in RRMM with t (11;14) and higher BCL-2/BCL-XL expression. BCMA CAR-T therapies have caused considerable remissions in highly refractory MM. These suggest that personalized medicine and therapy aiming at cure are becoming reality in the near future. MM is a genetically complex and heterogeneous disease that develops via a multistep transformation process. Recent next-generation sequencing (NGS) studies have revealed the molecular landscape, providing insights into the biology, including the intraclonal heterogeneity and disease progression in MM. In this review, we discuss the current knowledge regarding MM genomics reported by NGS studies as well as the recent progress in MM therapy. The agents and treatment reviewed here include elotuzumab, daratumumab, ixazomib, venetoclax, and BCMA CAR-T therapies.